Pharmacology 14-15 - Principle Of Antimicrobial Chemotherapy

Front 1

What is the procedure to empiric therapy?

Back 1

Clindamycin + gentamicin(effective against gram-(+) or imipenem/cilastin(single broad-spectrum antibiotic) ->culture bug -> use specific drug last

Front 2

What are the drugs used in Empiric therapy?

Back 2

Clindamycin + gentamicin or imipenem/cilastin

Front 3

Define: chemotherapy

Back 3

The use of chemical s against invading organisms (invading bacteria); NOTE: term is used for both treatment of infection and cancer

Front 4

Define: antibiotic

Back 4

Chemical that is produced by a microorganism and has the ability to harm other microbes

Front 5

Define: selective toxicity

Back 5

The ability of a drug (chemical) to injure a target cell or organism without injuring other cells or organisms that are in intimate contact

Front 6

How do u select the most appropriate anti-microbial agent?

Back 6

1. Organisms identity and its sensitivity to a particular agent, 2. site of infection, 3. safety of the agent, 4. patient factors, 5. cost of therapy

Front 7

Define: empiric therapy

Back 7

Use of antimicrobial agents before the pathogen is known; based on experience; justified if evidence demonstrates that early intervention will improve outcomes

Front 8

What is the most commonly used method to test susceptibility to antibiotics

Back 8

Disk diffusion test - disks containing antibiotics are placed on culture dishes inoculated w/the microorganism to be tested. Growth = resistance to bugs, no growth = sensitivity to bug

Front 9

Define: selective toxicity

Back 9

Kill the germs not the patient -> achieved by disruption of cell wall, protein synthesis, enzyme unique to bacteria

Front 10

What are the characteristics of selective toxicity?

Back 10

1. Unique target must be present in pathogen + absent in host, 2. Target must be structurally different in pathogen vs host, 3. Target must be more important in pathogen than in host

Front 11

What is the MOA of disruption of the bacterial cell wall

Back 11

Bacteria are encased in a rigid cell wall -> if disrupted bacteria would absorb water, swell, burst

Front 12

Which drugs target microbes cell wall -> thus promoting bacterial lysis?

Back 12

Penicillin and cephalosporins; b/c mammalian cells have no cell wall -> drugs directed at this structure do not affect the host

Front 13

What is the MOA of inhibition of an enzyme unique to bacteria

Back 13

Bacteria need to produce folic acid denovo -> sulfonamides inhibit bacteria production -> no PABA -> folic acid -> no division

Front 14

What drug inhibits bacterial de novo generation of folic acid?

Back 14

Sulfonamide

Front 15

What is the combination of drugs to target folic acid production?

Back 15

Sulphonamides(inhibits dihydropepteroate synthase) + trimethoprim(inhibits dihydrofolate reductase)

Front 16

What drugs cause disruption of cell wall membrane?

Back 16

Amphotericin B, ketoconazole

Front 17

What drugs cause bacteriostatic inhibitors of protein synthesis?

Back 17

Clindamycin, erythromycin, tetracyclines

Front 18

What drugs cause interference w/synthesis of bacterial DNA or RNA

Back 18

Fluoroquinolones, rifampin

Front 19

What drugs are anti-metabolites

Back 19

Flucytosine, sulfonamides, trimethoprim

Front 20

What drugs are viral enzyme inhibitors

Back 20

Acyclovir, zidovudine, saquinavir, indinavir

Front 21

What drugs are mycolic acid synthesis?

Back 21

Isoniazid

Front 22

What drugs have unknown mechanisms

Back 22

Amntadine, ethambutol, pyraziamide

Front 23

What drug is involved in the blockage of DNA twisting?

Back 23

Fluoroquinolones - thus blocks DNA gyrase from working

Front 24

What is the MOA of "unique" selective targeting?

Back 24

Drug targets genetic or biochemical pathway that is unique to pathogen(ie bacterial cell wall synthesis inhibitors)

Front 25

What is the MOA of "selective" selective targeting?

Back 25

Drugs targets protein isoform that is unique to pathogen(ie DHFR inhibitor)

Front 26

What is the MOA of "common" selective targeting?

Back 26

Drug targets metabolic requirement that is specific to pathogen(ie 5-Fluorouracil)

Front 27

Drugs that affect growth

Back 27

Bacterial static(tetracycline)

Front 28

Drugs that kill off the bactera

Back 28

Bacterialscidal(penicillin)

Front 29

What are the bactericidal drugs that we need to know?

Back 29

1. Bacitracin, 2. beta-lactams, 3. quinolones, 4. aminoglycosides, 5. polymyxins, 6. rifampin

Front 30

What are the bacteriostatic drugs that we need to know?

Back 30

1. Tetracycline, 2. sulfonamide, 3. trimethoprim, 4. chloramphenicol, 5. macrolide, 6. novobiocin, 7. clindamycin

Front 31

Define: minimum inhibitory concentration

Back 31

Anti-microbial should be present in concentrations such that it can either inhibit bacterial growth

Front 32

Define: minimum bactericidal concentration

Back 32

Kill the organism

Front 33

What are 3 factors that determine susceptibility and resistance of microorganisms to antimicrobial agents?

Back 33

1. Failure of drug to reach its target, 2. drug inactivation, 3. target alteration

Front 34

What is the MOA of entry for slow drug entry into a bacteria?

Back 34

Slow drug entry into a cell = via PORINs

Front 35

What is the MOA of gentamicin

Back 35

Targets ribosome -> actively transported across the cell membrane

Front 36

What is the MOA of resistance of gentamicin?

Back 36

1. Bacteria makes resistance by mutating the active transport mechanism of the drug, 2. anaerobic conditions slows entry into the cell

Front 37

What is the MOA of resistance of tetracyclines, chloramphenicol, fluoroquinolones, macrolides, beta-lactam antibiotics.

Back 37

Bacterial efflux pumps -> transports drugs out

Front 38

How do bacteria prevent entry of a drug into the cell?

Back 38

1. Mutation of porin causes blockage thus drug cant get in, 2. mutation in transport mechanism(active transport - gentamicin, efflux pump - tetracycline)

Front 39

How do lower urinary tract antibiotics get to its target site?

Back 39

The antibiotic is NOT metabolized in the body -> goes thru the blood -> into urine (intact) -> has effect

Front 40

How do bacteria inactivate aminoglycosides + beta-lactam antibiotics?

Back 40

Production of enzymes that modify or destroy the antibiotic (aka anti-penicillin protein)

Front 41

What drug is a prodrug that requires a bacterial enzyme to activate the drug?

Back 41

Isoniazid - mycobacterium tuberculosis activates the drug inside the bacteria(the bug is its own worst enemy)

Front 42

What is the MOA of Fluoroquinolones resistance?

Back 42

Utilizes mutation of natural target - gyrase mutation

Front 43

What is the MOA of macrolide and tetracycline resistance?

Back 43

Target modification - ribosomal protection

Front 44

What is the MOA of resistance of staphylococcal resistance to methicillin?

Back 44

Acquired resistant form of the susceptible target -> caused by production of low-affinity penicillin binding proteins(ie penicillin cant work on its target)

Front 45

Define: vertical acquisition of drug resistance

Back 45

Passage of trait to daughter cells

Front 46

Define: horizontal acquisition of drug resistance

Back 46

Between individual s by PLASMID EXCHANGE

Front 47

What are the advantages of horizontal gene transfer in bacteria?

Back 47

1. Avoids lethal mutation of essential genes, 2. level of resistance is higher -> caused by incremental change, 3. genes can be transferred to susceptible cells easily

Front 48

What is the MOA of streptomycin resistance?

Back 48

Ribosomal mutation

Front 49

What is the MOA of rifampin resistance?

Back 49

RNA polymerase mutation

Front 50

What is the MOA of linezolid resistance?

Back 50

Ribosomal RNA mutation

Front 51

How does high level resistance to a drug emerge?

Back 51

1. Sequential series of mutations(plasmids), 2. mutation that confers high-level resistance in a single step

Front 52

What is horizontal gene transfer

Back 52

Plasmid transfer of resistant genes

Front 53

Define: conjugation

Back 53

Direct transfer of resistant genes by cell-to-cell contact through a sex pilus or bridge(occurs in gram (-) bacilli + enterococci + staphylocicci)

Front 54

What is the requirements in bacteria that can under conjugation?

Back 54

R-factor

Front 55

How is antibiotic resistance is enhanced by natural selection

Back 55

Top selection (mixed resistance population) -> middle selection (only the strong survive) -> last selection -> only the strong replicate

Front 56

What is strep pneumoniae resistant to?

Back 56

Penicillin

Front 57

What is e coli resistant to?

Back 57

Fluoroquinolone

Front 58

What is staph aureus resistant to?

Back 58

vancomycin

Front 59

What is the problem w/broad spectrum antibiotics

Back 59

Sine broad spectrum antibiotics kill off more competing organisms than do narrow-spectrum drug, emergence of resistance is facilitated most by the broad-spectrum drugs

Front 60

Define: superinfection

Back 60

New infection that appears during the course of treatment for a primary infection -> new infection can develop b/c antibiotic use can eliminate the inhibitory influence of normal flora -> allowing a second infectious agent to flourish (common in broad-spectrum agents)

Front 61

How do you select antibiotics

Back 61

1. Identify organism, 2. drug sensitivity, 3. host factors

Front 62

What type of drugs are used to keep bacteria at bay in AIDS patients?

Back 62

Bactericidal

Front 63

How does meningitis impede drug access?

Back 63

BBB

Front 64

How does endocarditis impede drug access?

Back 64

Bacterial vegetation in the heart are difficult to penetrate

Front 65

How does infected abscesses impede drug access?

Back 65

Poor vascularity and the presence of pus and other material

Front 66

What are the 3 ways to get a drug across the BBB?

Back 66

1. Drug that readily crosses the BBB, 2. inject into subarachnoid space, 3. remove pus that hinders drug access

Front 67

Why do the elderly have high drug sensitivity?

Back 67

Reduced rates of drug metabolism + excretion -> leads to accumulation of antibiotics to toxic levels

Front 68

Why do neonates have high drug sensitivity?

Back 68

Poorly developed kidney and liver function -> eliminate drugs slowly

Front 69

What is the side effect of sulfonamides in newborns?

Back 69

New borns + sulfonamides = kernicterus(high levels of bilirubin)

Front 70

What is the side effect of tetracyclines in new borns?

Back 70

Binds to developing teeth -> causes discoloration of the teeth

Front 71

What is the side effect of gentamicin during pregnancy?

Back 71

Pregnancy + gentamicin -> irreversible hearing loss

Front 72

What is the side effect of anti-microbial drugs during pregnancy?

Back 72

Pregnancy + antimicrobial -> crosses placenta -> posing a risk to the developing fetus

Front 73

What is the side effect of tetracyclines during pregnancy?

Back 73

Pregnancy + tetracycline -> hepatic necrosis, pancreatitis, renal damage

Front 74

What is the side effect of sulfonamides in breast milk?

Back 74

Sulfonamide + breast feeding -> enters breast milk

Front 75

Which antibiotics have a chance of severe allergic reaction

Back 75

1. Penicillin, 2. sulfonamide, 3. trimethoprim, 3. erythromycin

Front 76

What is the side effect of sulfonamides in G6PD deficient people?

Back 76

Hemolysis

Front 77

What are the reasons to use anti-biotic combinations?

Back 77

1. Initial therapy of severe infection, 2. mixed infection, 3. prevention of resistance, 4. ↓ toxicity, 5. enhanced anti-bacterial action

Front 78

What are the 3 possible effects by using 2 antibiotics in combination?

Back 78

1. Additive, 2. potentiative(aka synergistic), 3 .antagonistic(static agent is antagonistic to cidal agent

Front 79

What is the MOA of an additive response?

Back 79

Antimicrobial effect of combination = the sum of the effects of the two drugs alone(ie 2 bacteriostatic agents w/same MOA)

Front 80

What is the MOA of a potentiative (synergistic) response?

Back 80

Effect of the combination is greater then the sum of the effects of the individual agent(shows a 4x ↑ in antibacterial activity aka ↓ in MIC by 1/4)

Front 81

What are the 3 mechanisms of antibiotic synergism?

Back 81

1. Blockade of sequential steps(trimethoprim + sulfamethoxazole, 2. inhibition of enzyme(beta-lactam + beta-lactamase inhibitor sulbactam), 3. enhancement of AB uptake(penicillin ↑ uptake of aminoglycoside)

Front 82

Define: mixed infections

Back 82

Infections that may be caused by more than one microbe -> common in brain abscesses, pelvic infection, and infections from perforation of abdominal organs.

Front 83

How does the combination of flucytosine + amphotericin B work?

Back 83

Decreased toxicity -> treats fungal meningitis (prevents risk of amphotericin-induced damage to kidney)

Front 84

How does the combination of penicillin + aminoglycoside work?

Back 84

Enhanced antibacterial action - penicillin weakens bacterial wall + aminoglycoside suppresses protein synthesis

Front 85

When do u use prophylactic antibiotics?

Back 85

Surgery, congentital abnormalities, neutropenia

Front 86

What are the misuses of antibiotics

Back 86

1. Viral infection, 2. fever of unknown origin, 3. improper dosage

Front 87

What group of drugs is amoxicillin in?

Back 87

Penicillins

Front 88

What group of drugs is tetracycline in?

Back 88

Tetracyclines

Front 89

What group of drugs is streptomycin in?

Back 89

Aminoglycosides

Front 90

What group of drugs is levofloxacin in?

Back 90

Quinolones

Front 91

What group of drugs is cefaclor in?

Back 91

Cephalosporins

Front 92

What group of drugs is erythromycin in?

Back 92

Macrolides

Front 93

What is the MOA of amoxicillin?

Back 93

Binds to Penicillin binding proteins

Front 94

What is the MOA of tetracycline?

Back 94

30S ribosome

Front 95

What is the MOA of sterptomycin?

Back 95

Affects protein synthesis

Front 96

What is the MOA of levofloxacin?

Back 96

DNA gyrase inhibitors

Front 97

What is the MOA of cefaclor?

Back 97

Protein synthesis

Front 98

What is the MOA of erythromycin?

Back 98

50S ribosome